A research team led by Carnegie Mellon University's Sheldon Cohen has found that chronic psychological stress is associated with the body losing its ability to regulate the inflammatory response

"Inflammation is partly regulated by the hormone cortisol and when cortisol is not allowed to serve this function, inflammation can get out of control,"

Essentially, the immune system becomes less responsive to Cortisol's balancing act if it's always present.

Very similar to our body's response to constant sugar...diabetes!

They went on to say...

When under stress, cells of the immune system are unable to respond to hormonal control, and consequently, produce levels of inflammation that promote disease.

Other studies have showed this same effect with cortisol having so called "biphasic" effects on inflammation.

Excessive cortisol (from chronic stress) poses its own issues in terms of anxiety:

Exaggerated or recurrent negative cognitions, rumination or worry, magnification, and helplessness are all maladaptive catastrophizing responses to pain or non–pain-related stress that may prolong cortisol secretion

Scientists have learned that animals that experience prolonged stress have less activity in the parts of their brain that handle higher-order tasks — for example, the prefrontal cortex — and more activity in the primitive parts of their brain that are focused on survival, such as the amygdala.

In fact, recent research showed that THC thickens the amygdala in such a manner.

The biggest differences in gray matter were in the amygdala, which is involved in fear and other emotion-related processes, and in the hippocampus, involved in memory development and spatial abilities.

Remember that powerful thoroughfare of communication between our scaredy cat (amygdala) and voice of reason, the prefrontal cortex.

The uncinate fasciculus (say that 5 times fast).

Chronic stress early in life can affect this communication link as well:

Exposure to intense and chronic stressors during the developmental years has long-lasting neurobiological effects and puts one at increased risk for anxiety and mood disorders

When that bike is about to crash into you, calm is not the response that will keep you (or your ancestors) alive.

Adrenaline and Cortisol is more needed!

Long term, chronic stress however will depress GABA levels which is directly tied to anxiety.

Chronic stress causes disinhibition of the hypothalamus-pituitary-adrenal axis. Consequently, the brain is overexposed to glucocorticoids which in humans may precipitate stress-related disorders, e.g. depression.

What about serotonin (more tied to depression but also present with anxiety circuit).

An interesting study showed that in health subjects, cortisol (our main stressor chemical) would boost serotonin but not in subjects with depression or anxiety:

A significant increase in serotonin uptake (+37% + 14, M + SD) was observed in the control group, whereas neither the generalized anxiety disorder nor the major depression group exhibited changes in serotonin uptake upon incubation with cortisol.

The various chemicals interact at specific receptors throughout the brain and body known as CB1 and CB2 receptors.

The research went on to say:

Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a downregulation or loss of cannabinoid type 1 (CB1) receptors.

Let's put the pieces all together now:

With respect to the functional role of changes in eCB signaling during stress, studies have demonstrated that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic–pituitary–adrenal (HPA) axis and increases in anxiety behavior

Put a note next to Anandamide for when we discuss CBD below (very exciting).

Back to the question we had at the beginning...why do some people have one stress response while another person has a completely different stress response?

translational studies have shown that eCB signaling in humans regulates many of the same domains and appears to be a critical component of stress regulation, and impairments in this system may be involved in the vulnerability to stress-related psychiatric conditions, such as depression and posttraumatic stress disorder.

However, during times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically.[3] This may result in significant damage to cell structures.

Collateral damage to surrounding tissue and since it's in the brain, that's valuable real estate.

To be more specific:

They also trigger numerous molecular cascades, leading to increased blood-brain barrier permeability (through activation of matrix metalloproteinases and subsequently degradation of tight junctions), alterations of brain morphology, neuroinflammation, and neuronal death

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